Aging exacerbates the response of the central nervous system to injury, leading to higher morbidity and mortality after traumatic brain injury (TBI) in elderly individuals compared with younger adults. Mechanisms of brain injury are altered with age, suggesting that a different approach to treatment might be required in older patients. However, nearly all drug development studies for TBI have been in young adult animals. Taurine, an abundant amino acid in the brain, has multiple neuroprotective properties including osmoregulation, anti-oxidative, anti-inflammatory, and anti-apoptotic effects. We have found that brain taurine levels decrease after TBI in rats, and that this effect is more severe in elderly animals than in younger adults. Treatment with exogenous taurine improves recovery and reduces neuronal death after TBI in adult rats; however the neuroprotective efficacy of taurine in older animals is unknown. Given the evidence that taurine can ameliorate brain edema, oxidative stress, and inflammation, and apoptosis - all mechanisms of injury that are worse in the aged brain - taurine is a promising novel treatment for TBI in the elderly. We propose a series of studies to establish the therapeutic efficacy of taurine and to confirm its mechanism(s) of action in aged rats after cortical contusion injury.
Our Specific Aims are: (1) To determine the effects of taurine treatment on neuroimaging biomarkers and behavioral and tissue outcomes in aged rats after TBI, and (2) To confirm mechanisms of taurine action in aged rats after TBI. We predict that taurine treatment will improve functional outcome, reduce the brain contusion size, and attenuate changes in neuroimaging biomarkers after TBI in aged rats. We anticipate that the neuroprotective mechanisms of taurine in aged rats will include reduction of cerebral edema, oxidative stress, neuroinflammation, and apoptosis. This proposal addresses the NINDS objective for R21 Exploratory/Developmental grants, which supports projects in translational research intended to identify and develop candidate therapeutics to reduce the burden of neurological disease. We expect that the successful completion of these studies will yield evidence that taurine is neuroprotective after TBI in aged rats, and provide further insight into mechanisms of action. Non- invasive imaging biomarkers of specific drug effects may facilitate future translation from preclinical to clinical studies. Results from the current projec will be important for justifying further development of taurine as a treatment in older human survivors of TBI, with the ultimate goal of improving outcomes in this vulnerable population.

Public Health Relevance

Outcomes after traumatic brain injury (TBI) are worse in older patients than in younger adults, but little research has focused on how to treat TBI in the aging brain. Taurine is a highly promising candidate treatment for improving outcome after injury due to its multiple mechanisms of neuroprotection. These studies will establish the therapeutic efficacy of taurine and confirm its mechanism(s) of action after TBI in aged rats.